Research ArticleFibrosis

Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis

See allHide authors and affiliations

Science Translational Medicine  13 Dec 2017:
Vol. 9, Issue 420, eaal3765
DOI: 10.1126/scitranslmed.aal3765

Reversing fibrosis through apoptosis

Myofibroblasts are integral in a feedback loop that perpetuates fibrosis through stiffening of the extracellular matrix. Lagares et al. determined that proapoptotic proteins are increased in these stiffness-activated myofibroblasts, and these cells become dependent on antiapoptotic protein expression to prevent their death. A drug that mimics a proapoptotic protein to block the antiapoptotic protein BCL-XL induced apoptosis in fibroblasts from patients with scleroderma, a fibrotic connective tissue disorder. The drug, ABT-263, was also effective in reversing established fibrosis in a mouse model of scleroderma. This study suggests that targeting antiapoptotic proteins to induce myofibroblast apoptosis could be an effective strategy to treat fibrosis.

View Full Text

Stay Connected to Science Translational Medicine